scholarly journals Hypertension, a Moving Target in COVID-19

2021 ◽  
Vol 128 (7) ◽  
pp. 1062-1079
Author(s):  
Carmine Savoia ◽  
Massimo Volpe ◽  
Reinhold Kreutz
Keyword(s):  
Global Health ◽  
Angiotensin Receptor Blockers ◽  
Experimental Studies ◽  
Renin Angiotensin System ◽  
Host Cells ◽  
High Rate ◽  
Direct Role ◽  
Pressure Lowering ◽  
Ras Blockers

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associates with a considerable high rate of mortality and represents currently the most important concern in global health. The risk of more severe clinical manifestation of COVID-19 is higher in males and steeply raised with age but also increased by the presence of chronic comorbidities. Among the latter, early reports suggested that arterial hypertension associates with higher susceptibility to SARS-CoV-2 infection, more severe course and increased COVID-19–related deaths. Furthermore, experimental studies suggested that key pathophysiological hypertension mechanisms, such as activation of the renin-angiotensin system (RAS), may play a role in COVID-19. In fact, ACE2 (angiotensin-converting-enzyme 2) is the pivotal receptor for SARS-CoV-2 to enter host cells and provides thus a link between COVID-19 and RAS. It was thus anticipated that drugs modulating the RAS including an upregulation of ACE2 may increase the risk for infection with SARS-CoV-2 and poorer outcomes in COVID-19. Since the use of RAS-blockers, ACE inhibitors or angiotensin receptor blockers, represents the backbone of recommended antihypertensive therapy and intense debate about their use in the COVID-19 pandemic has developed. Currently, a direct role of hypertension, independent of age and other comorbidities, as a risk factor for the SARS-COV-2 infection and COVID-19 outcome, particularly death, has not been established. Similarly, both current experimental and clinical studies do not support an unfavorable effect of RAS-blockers or other classes of first line blood pressure lowering drugs in COVID-19. Here, we review available data on the role of hypertension and its management on COVID-19. Conversely, some aspects as to how the COVID-19 affects hypertension management and impacts on future developments are also briefly discussed. COVID-19 has and continues to proof the critical importance of hypertension research to address questions that are important for global health.

The Role of Angiotensin-(1-7)/Mas Axis and Angiotensin Type 2 Receptors in the Central Nervous System in Cardiovascular Disease and Therapeutics: A Riddle to be Solved

2019 ◽  
Vol 17 (4) ◽  
pp. 319-325 ◽  
Author(s):  
Vasiliki Katsi ◽  
Spyridon Maragkoudakis ◽  
Maria Marketou ◽  
Costas Tsioufis ◽  
Fragkiskos Parthenakis ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Experimental Studies ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Pressure Lowering ◽  
The Central Nervous System ◽  
Novel Therapeutic Strategies ◽  
Angiotensin Type

: In recent years, the Angiotensin-(1-7)/Mas receptor [Ang-(1-7)/Mas] sub-branch of the Renin-Angiotensin System (RAS) in the brain, and Angiotensin Type 2 Receptors (AT2R), have attracted scientific interest, as there is evidence that they constitute an essential pathway in cardiovascular regulation, in health and in disease. By acting centrally, the Ang-(1-7)/Mas axis - that has been termed ‘the axis of good’- can exert blood pressure-lowering effects, while also favourably altering baroreflex sensitivity and noradrenergic neurotransmission. Thus, research has focused on the possible neuro- and cardioprotective effects of this pathway in the setting of cardiovascular disease, ultimately aiming to evaluate the potential for development of novel therapeutic strategies based on its modulation. : We summarize the available evidence from experimental studies in this context, aiming to assess current limits of scientific knowledge relevant to this newly-described ‘player’ in haemodynamic regulation, that may become a potential therapeutic target.

Effects of perfusate buffer capacity on capillary CO2-HCO3(-)-H+ reactions: theory

1991 ◽  
Vol 71 (4) ◽  
pp. 1460-1468 ◽  
Author(s):  
A. Bidani ◽  
T. A. Heming
Keyword(s):  
Carbonic Anhydrase ◽  
Buffer Capacity ◽  
Experimental Studies ◽  
Nonlinear Effects ◽  
Co2 Exchange ◽  
High Rate ◽  
Pulmonary Capillaries ◽  
Sequential Combination ◽  
Time Courses

The importance of perfusate nonbicarbonate buffer capacity (beta nonHCO3) to intracapillary CO2-HCO3(-)-H+ reactions was assessed by theoretical analysis of CO2 exchange in saline-perfused pulmonary capillaries. Time courses for perfusate PCO2, [HCO3-], and [H+] were computed for capillaries containing different activities of luminal vascular carbonic anhydrase and different amounts of perfusate nonbicarbonate buffers. Mobilization of perfusate HCO3- toward CO2 during capillary transit is determined by the availability of HCO3- and H+. A supply of protons from the nonbicarbonate buffer pool is necessary to maintain a high rate of HCO3- dehydration. The analyses indicate that beta nonHCO3 has marked nonlinear effects on transcapillary CO2 exchange and intravascular pH equilibration. These nonlinear effects differ from those previously computed for CO2 reactions in an open system because the present model system consists of a sequential combination of open (within capillary proper) and closed (within postcapillary vasculature) systems. The role of luminal vascular carbonic anhydrase in capillary CO2 reactions is strongly dependent on beta nonHCO3. Perfusate nonbicarbonate buffer capacity must be considered when the results of experimental studies of transcapillary CO2 exchange and/or intravascular pH equilibration are interpreted.

scholarly journals Renin-Angiotensin-System (RAS) und COVID-19 – Zur Verordnung von RAS-Blockern

2020 ◽  
Vol 145 (10) ◽  
pp. 682-686 ◽  
Author(s):  
Reinhold Kreutz ◽  
Engi Abd El-Hady Algharably ◽  
Detlev Ganten ◽  
Franz Messerli
Keyword(s):  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Short Review ◽  
Angiotensin Receptor ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Analysis And Evaluation ◽  
Receptor Blockers ◽  
Ras Blockers ◽  
Regulatory Functions

AbstractTwenty years ago, an enzyme homologous to the previously known angiotensin-converting enzyme (ACE) was identified, and subsequently named ACE2. In the renin-angiotensin system (RAS), ACE2 has counter-regulatory functions against the classical effector peptide angiotensin II, for example in blood pressure regulation and cardiovascular remodeling. However, ACE2 provides an initially unexpected interesting link between virology and cardiovascular medicine. That is, ACE2 represents the binding receptor for the cellular uptake of SARS-CoV and SARS-CoV-2 viruses. Thus, ACE2 is relevant for COVID-19. In this context, it was suspected that therapy with RAS blockers might promote transmission and complications of COVID-19 by upregulation of ACE2 expression. The aim of this short review is, to describe the link between the RAS, particularly ACE2, and COVID-19. Based on our analysis and evaluation of the available findings, we justify our conclusion: important drugs such as ACE inhibitors and angiotensin receptor blockers should continue to be prescribed according to guidelines to stable patients in the context of the COVID-19 pandemic.

scholarly journals The Genomics of Myelodysplastic Syndromes: Origins of Disease Evolution, Biological Pathways, and Prognostic Implications

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2512
Author(s):  
Hassan Awada ◽  
Bicky Thapa ◽  
Valeria Visconte
Keyword(s):  
Experimental Studies ◽  
Gene Mutations ◽  
High Rate ◽  
Murine Models ◽  
Disease Evolution ◽  
Molecular Alterations ◽  
Disease Phenotypes ◽  
Prognostic Implications ◽  
Made In

The molecular pathogenesis of myelodysplastic syndrome (MDS) is complex due to the high rate of genomic heterogeneity. Significant advances have been made in the last decade which elucidated the landscape of molecular alterations (cytogenetic abnormalities, gene mutations) in MDS. Seminal experimental studies have clarified the role of diverse gene mutations in the context of disease phenotypes, but the lack of faithful murine models and/or cell lines spontaneously carrying certain gene mutations have hampered the knowledge on how and why specific pathways are associated with MDS pathogenesis. Here, we summarize the genomics of MDS and provide an overview on the deregulation of pathways and the latest molecular targeted therapeutics.

scholarly journals Gut microbiomes and reproductive isolation in Drosophila

2017 ◽  
Vol 114 (48) ◽  
pp. 12767-12772 ◽  
Author(s):  
Philip T. Leftwich ◽  
Naomi V. E. Clarke ◽  
Matthew I. Hutchings ◽  
Tracey Chapman
Keyword(s):  
Reproductive Isolation ◽  
Assortative Mating ◽  
Gut Microbiome ◽  
Experimental Studies ◽  
Gut Bacteria ◽  
Evolutionary Significance ◽  
Direct Role ◽  
General Role ◽  
Positive Assortative Mating

Experimental studies of the evolution of reproductive isolation (RI) in real time are a powerful way in which to reveal fundamental, early processes that initiate divergence. In a classic speciation experiment, populations of Drosophila pseudoobscura were subjected to divergent dietary selection and evolved significant positive assortative mating by diet. More recently, a direct role for the gut microbiome in determining this type of RI in Drosophila melanogaster has been proposed. Manipulation of the diet, and hence the gut microbiome, was reported to result in immediate assortative mating by diet, which could be eliminated by reducing gut microbes using antibiotics and recreated by adding back Lactobacillus plantarum. We suggest that the evolutionary significance of this result is unclear. For example, in D. melanogaster, the microbiome is reported as flexible and largely environmentally determined. Therefore, microbiome-mediated RI would be transient and would break down under dietary variation. In the absence of evolutionary coassociation or recurrent exposure between host and microbiome, there are no advantages for the gut bacteria or host in effecting RI. To explore these puzzling effects and their mechanisms further, we repeated the tests for RI associated with diet-specific gut microbiomes in D. melanogaster. Despite observing replicable differences in the gut microbiomes of flies maintained on different diets, we found no evidence for diet-associated RI, for any role of gut bacteria, or for L. plantarum specifically. The results suggest that there is no general role for gut bacteria in driving the evolution of RI in this species and resolve an evolutionary riddle.

scholarly journals Cessation of Renin-Angiotensin System Antagonists During the SARS-CoV-2 Pandemic – Do We Have the Evidence?

2020 ◽  
Vol 5 (3) ◽  
pp. 105-109
Author(s):  
Emanuel Blîndu ◽  
Renata Gerculy ◽  
Diana Opincariu ◽  
Daniel Cernica ◽  
Imre Benedek
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blockers ◽  
Healthcare Providers ◽  
Age Groups ◽  
Renin Angiotensin System ◽  
Host Cells ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin

AbstractThe aim of this review is to provide a short update on whether treatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) has beneficial or harmful effects in patients infected with SARS-CoV-2. Epidemiological studies have shown that SARS-CoV-2 infects all age groups, presenting a higher incidence in elderly patients with various comorbidities such as hypertension, diabetes mellitus, and cardiovascular diseases. A large proportion of these patients are treated with ACEIs and ARBs. Since it has been demonstrated that SARS-CoV-2 uses angiotensin converting enzyme type 2 (ACE2) as an entry point into host cells, it is important to know whether ACEIs and ARBs could modify the expression of this enzyme, and thus promote the viral infection. Animal studies and a few studies in humans have shown that renin angiotensin system (RAS) inhibitors increase tissue expression of ACE2, but with potentially beneficial effects. In this context, it is imperative to provide appropriate guidance for clinicians and patients. The major cardiology associations across the world have released statements in which they recommend healthcare providers and patients to continue their treatments for hyper-tension and heart failure as prescribed.

scholarly journals The Controversy on the Role of ACE2 Receptor in COVID-19 Infection: The Protective Shift toward the ACE2 Axis

2020 ◽  
Author(s):  
Sarah I Y Ahmed
Keyword(s):  
Animal Studies ◽  
Experimental Studies ◽  
Renin Angiotensin System ◽  
Protective Role ◽  
Genetic Variations ◽  
Converting Enzyme ◽  
Organ Protection ◽  
Angiotensin Converting Enzyme 2 ◽  
Scientific Debate

Background: Angiotensin-converting enzyme 2 (ACE2)  is recognized as the main cellular receptor for the new coronavirus, SARS-CoV-2, that facilitates its entry into the host target cell, leading to the fatal viral infection, coronavirus disease 2019 (COVID-19). Thus, it is considered as a main therapeutic target in the SARS-CoV-2 infection. The dual role of ACE2 as a gate for SARS-CoV-2 virus and as a part of lung and multi-organ protection has built a scientific debate that affects the choice of treatments used against COVID-19 patient. ACE2 inhibitors like anti-ACE2 antibodies were first introduced as therapeutic solutions that, theoretically, would decrease the availability of target molecules for SARS-CoV-2 by downregulating ACE2 expression. However, animal studies showed that ACE2 upregulation acts as a counterbalance to the hypertensive pro-inflammatory angiotensin I-converting enzyme (ACE) in the renin–angiotensin system (RAS) and results in a protective role against acute lung injury – a fatal consequence of the disease. The current study tests the effect of ACE2-activating treatments against the outcome of genetic variations in the population that have ACE2-upregulatory effects. Conclusion  Despite its role as a receptor for the SARS-CoV-2 virus, experimental studies and the genetic polymorphisms in populations that have ACE2 upregulation revealed a protective role against COVID-19 infection.   Key words: ACE2   ACE  COVID-19  treatments  genetic variations

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